Phase I Dose Escalation Study of N-Acetylcysteine Administered in Conjunction With Carboplatin, Cyclophosphamide, and Etoposide Phosphate BBBD, in Children With Malignant Brain Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- To assess toxicity and the maximally tolerated dose of N-acetylcysteine administered in conjunction with carboplatin, cyclophosphamide and etoposide phosphate BBBD, and delayed high dose sodium thiosulfate, in children with malignant brain tumors.
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, etoposide phosphate, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Mannitol may help chemotherapy work better by making it easier for these drugs to get to the tumor. Chemoprotective drugs, such as acetylcysteine and sodium thiosulfate, may protect normal cells from the side effects of chemotherapy. Giving acetylcysteine together with mannitol, combination chemotherapy, and sodium thiosulfate may be an effective treatment for malignant brain tumors.
PURPOSE: This phase I trial is studying the side effects and best dose of acetylcysteine when given together with mannitol, combination chemotherapy, and sodium thiosulfate in treating children with malignant brain tumors.
详细描述
OBJECTIVES:
Primary
- Determine the toxicity and maximum tolerated dose of acetylcysteine when given in combination with blood-brain barrier disruption treatment with mannitol, combination chemotherapy comprising cyclophosphamide, etoposide phosphate, and carboplatin, and delayed high-dose sodium thiosulfate in pediatric patients with malignant brain tumors.
Secondary
- Determine the blood/bone marrow toxicity of this regimen in these patients.
- Determine tumor response in patients treated with this regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed brain tumors, including any of the following:
- •Brain stem glioma
- •Primitive neuroectodermal tumor
- •CNS germ cell tumor
- •Malignant glioma
- •Diagnosis based on any of the following:
- •CT-assisted or stereotactic biopsy
- •Open biopsy
- •Surgical resection
- •Cerebrospinal fluid cytology
- •Elevated tumor markers
- •Unequivocal radiographic changes (for patients with brain stem glioma or optic glioma)
- •All tumor types, except brain stem glioma, must be recurrent
- •No radiographic signs of intracranial herniation and/or spinal cord block
- •PATIENT CHARACTERISTICS:
- •Performance status
- •Life expectancy
- •At least 90 days
- •Hematopoietic
- •WBC ≥ 2,500/mm^3
- •Absolute granulocyte count ≥ 1,200/mm^3
- •Platelet count ≥ 100,000/mm^3
- •SGOT and SGPT < 2.5 times upper limit of normal
- •Bilirubin < 2.0 mg/dL
- •Creatinine < 1.8 mg/dL
- •No history of clinically significant reactive airway disease
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No significant risk for general anesthesia
- •No uncontrolled, clinically significant, confounding medical condition within the past 30 days
- •No contraindication to study drugs
- •PRIOR CONCURRENT THERAPY:
- •Chemotherapy
- •At least 28 days since prior systemic chemotherapy
- •Radiotherapy
- •At least 3 months since prior total spine radiotherapy
- •At least 14 days since prior cranial radiotherapy
- •Prior systemic radiotherapy allowed
- •See Disease Characteristics
排除标准
- 未提供
结局指标
主要结局
To assess toxicity and the maximally tolerated dose of N-acetylcysteine administered in conjunction with carboplatin, cyclophosphamide and etoposide phosphate BBBD, and delayed high dose sodium thiosulfate, in children with malignant brain tumors.
次要结局
未报告次要终点
研究者
Edward Neuwelt
Professor
OHSU Knight Cancer Institute